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Genome-wide association studies suggest sex-specific loci associated with abdominal and visceral fat.
Sung YJ, Pérusse L, Sarzynski MA, Fornage M, Sidney S, Sternfeld B, Rice T, Terry JG, Jacobs DR, Katzmarzyk P, Curran JE, Jeffrey Carr J, Blangero J, Ghosh S, Després JP, Rankinen T, Rao DC, Bouchard C
(2016) Int J Obes (Lond) 40: 662-74
MeSH Terms: Adult, African Americans, Body Mass Index, Cardiovascular Diseases, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intra-Abdominal Fat, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Sex Characteristics, Sex Factors, Subcutaneous Fat, Abdominal, United States
Show Abstract · Added October 23, 2015
BACKGROUND - To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
SUBJECTS AND METHODS - Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
RESULTS - A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P<1.0 × 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P=1.10 × 10(-7)), an association that was replicated (P=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P=2.42 × 10(-7)). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10(-8) to 1.13 × 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively.
CONCLUSIONS - Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.
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18 MeSH Terms
Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.
Wainright KS, Fleming NJ, Rowles JL, Welly RJ, Zidon TM, Park YM, Gaines TL, Scroggins RJ, Anderson-Baucum EK, Hasty AH, Vieira-Potter VJ, Padilla J
(2015) Am J Physiol Regul Integr Comp Physiol 309: R594-602
MeSH Terms: Adipokines, Adiposity, Age Factors, Animals, Disease Models, Animal, Eating, Endoplasmic Reticulum Stress, Gene Expression Regulation, Inflammation Mediators, Intra-Abdominal Fat, Male, Mice, Inbred C57BL, Motor Activity, Obesity, Oxidative Stress, Phenotype, Running, Sedentary Behavior
Show Abstract · Added September 28, 2015
Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype.
Copyright © 2015 the American Physiological Society.
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18 MeSH Terms
DXA-measured visceral adipose tissue predicts impaired glucose tolerance and metabolic syndrome in obese Caucasian and African-American women.
Bi X, Seabolt L, Shibao C, Buchowski M, Kang H, Keil CD, Tyree R, Silver HJ
(2015) Eur J Clin Nutr 69: 329-36
MeSH Terms: Absorptiometry, Photon, Adult, African Americans, Anthropometry, Body Composition, Cardiovascular Diseases, European Continental Ancestry Group, Female, Glucose Intolerance, Humans, Intra-Abdominal Fat, Metabolic Syndrome, Obesity, Risk Factors
Show Abstract · Added July 30, 2015
BACKGROUND/OBJECTIVES - New methods to measure visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed (1) to compare relationships of DXA-VAT, anthropometric and body composition variables with cardiometabolic risk factors in obese women; (2) to determine which variables most robustly predict impaired glucose tolerance (IGT) and metabolic syndrome (MetSx); and (3) to determine thresholds for DXA-VAT by race.
SUBJECTS/METHODS - VAT mass (g) and volume (cm(3)) were measured in 229 obese (body mass index (BMI), 30-49.9) women aged 21-69 years of European-American (EA=123) and African-American (AA=106) descent using the CoreScan algorithm on a Lunar iDXA scanner. Linear regression modeling and areas under the curve (AUC of ROC (receiver operating characteristic) curves) compared relationships with cardiometabolic risk. Bootstrapping with LASSO (least absolute shrinkage and selection operator) regression modeling determined thresholds and predictors of IGT and MetSx.
RESULTS - DXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and homeostatic model assessment-insulin resistance (HOMA-IR) compared with anthropometric and other body composition variables. DXA-VAT also had the highest AUC for IGT (0.767) and MetSx (0.749). Including race as a variable and the interaction between VAT and race in modeling did not significantly change the results. Thresholds at which the probability of developing IGT or MetSx was⩾50% were determined separately for AA women (IGT: 2120 cm(3); MetSx: 1320 cm(3)) and EA women (IGT: 2550 cm(3); MetSx: 1713 cm(3)). The odds for IGT or MetSx were fourfold greater with each standard deviation increase in DXA-VAT.
CONCLUSIONS - DXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA obese women and offers potential utility in the risk reduction interventions.
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14 MeSH Terms
Associations between nonalcoholic fatty liver disease and subclinical atherosclerosis in middle-aged adults: the Coronary Artery Risk Development in Young Adults Study.
VanWagner LB, Ning H, Lewis CE, Shay CM, Wilkins J, Carr JJ, Terry JG, Lloyd-Jones DM, Jacobs DR, Carnethon MR
(2014) Atherosclerosis 235: 599-605
MeSH Terms: Adult, Aorta, Abdominal, Aortic Diseases, Atherosclerosis, Coronary Artery Disease, Coronary Vessels, Female, Humans, Intra-Abdominal Fat, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Tomography, X-Ray Computed, Vascular Calcification, Young Adult
Show Abstract · Added June 30, 2014
OBJECTIVE - Non-alcoholic fatty liver disease (NAFLD) is an obesity-related condition associated with cardiovascular mortality. Yet, whether or not NAFLD is independently related to atherosclerosis is unclear. In a population-based cross-sectional sample of middle-aged adults free from liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical atherosclerosis (coronary artery (CAC) and abdominal aortic calcification (AAC)) independent of obesity.
METHODS - Participants from the Coronary Artery Risk Development in Young Adults study with CT quantification of liver fat, CAC and AAC were included (n = 2424). NAFLD was defined as liver attenuation ≤40 Hounsfield Units after exclusion of other causes of liver fat. CAC and AAC presence was defined as Agatston score >0.
RESULTS - Mean participant age was 50.1 ± 3.6 years, (42.7% men, 50.0% black) and BMI was 30.6 ± 7.2 kg/m(2). The prevalence of NAFLD, CAC, and AAC was 9.6%, 27.1%, and 51.4%. NAFLD participants had increased prevalence of CAC (37.9% vs. 26.0%, p < 0.001) and AAC (65.1% vs. 49.9%, p < 0.001). NAFLD remained associated with CAC (OR, 1.33; 95% CI, 1.001-1.82) and AAC (OR, 1.74; 95% CI, 1.29-2.35) after adjustment for demographics and health behaviors. However, these associations were attenuated after additional adjustment for visceral adipose tissue (CAC OR, 1.05; 95% CI, 0.74-1.48, AAC OR = 1.20; 95% CI, 0.86-1.67). There was no interaction by race or sex.
CONCLUSION - In contrast to prior research, these findings suggest that obesity attenuates the relationship between NAFLD and subclinical atherosclerosis. Further studies evaluating the role of NAFLD duration on atherosclerotic progression and cardiovascular events are needed.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
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15 MeSH Terms
Associations of body size and body composition with functional ability and quality of life in hemodialysis patients.
Martinson M, Ikizler TA, Morrell G, Wei G, Almeida N, Marcus RL, Filipowicz R, Greene TH, Beddhu S
(2014) Clin J Am Soc Nephrol 9: 1082-90
MeSH Terms: Adult, Aged, Body Composition, Body Mass Index, Exercise Test, Exercise Tolerance, Female, Humans, Intra-Abdominal Fat, Magnetic Resonance Imaging, Male, Middle Aged, Quadriceps Muscle, Quality of Life, Renal Dialysis, Surveys and Questionnaires, Waist Circumference
Show Abstract · Added September 29, 2014
BACKGROUND AND OBJECTIVES - Modifiable factors, such as body size and body composition, could influence physical function and quality of life in patients undergoing maintenance hemodialysis (MHD).
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS - From January 2008 to June 2012, in body mass index (BMI), waist circumference (WC), and magnetic resonance imaging measurements of midthigh muscle area (MTMA) and intra-abdominal fat area (IAFA) were obtained at baseline in 105 MHD patients. Six-minute walk distances and physical and mental component scores (PCS and MCS) from the Short Form-12 questionnaire were obtained at baseline and 6 and 12 months. Separate mixed-effects regression models were used to relate baseline BMI, WC, and IAFA with baseline and the average of follow-up 6-minute walk distances and PCS and MCS after adjustment for baseline covariates and MTMA.
RESULTS - for baseline covariates and baseline MTMA, each SD increase in baseline BMI was inversely associated with baseline (-31.5 m; 95% confidence interval [95% CI], -53.0 to -10.0 m) and follow-up (-36.9 m; 95% CI, -54.6 to -19.2 m) 6-minute walk distances. Results were similar for WC and IAFA. In each of these models, each SD increase in MTMA had a strong positive association with 6-minute walk distance. Adiposity measures were not associated with baseline or follow-up PCS and MCS. After adjustment for baseline BMI, each SD increase in baseline MTMA was associated with higher baseline PCS score (3.78; 95% CI, 0.73 to 6.82) and MCS (3.75; 95% CI, 0.44 to 7.05) but had weaker associations with follow-up PCS and MCS.
CONCLUSIONS - Body size and composition are significantly associated with physical functioning and quality of life. Interventions that improve muscle mass and decrease obesity might improve these measures in patients undergoing MHD.
Copyright © 2014 by the American Society of Nephrology.
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17 MeSH Terms
Comparison of gross body fat-water magnetic resonance imaging at 3 Tesla to dual-energy X-ray absorptiometry in obese women.
Silver HJ, Niswender KD, Kullberg J, Berglund J, Johansson L, Bruvold M, Avison MJ, Welch EB
(2013) Obesity (Silver Spring) 21: 765-74
MeSH Terms: Absorptiometry, Photon, Adipose Tissue, Adiposity, Adult, Anthropometry, Body Mass Index, Female, Humans, Intra-Abdominal Fat, Linear Models, Magnetic Resonance Imaging, Middle Aged, Obesity, Young Adult
Show Abstract · Added May 29, 2013
OBJECTIVE - Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional (3D) contiguous "fat-water" MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology.
DESIGN AND METHODS - Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to dual-energy X-ray absorptiometry (DXA). Anthropometric, FWMRI, and DXA measurements were obtained in 12 women with BMI 30-39.9 kg/m(2) .
RESULTS - Test-retest results found coefficients of variation (CV) for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST, and TTLST, respectively.
CONCLUSIONS - While Bland-Altman plots demonstrated agreement between FWMRI and DXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30-min total scan and post-processing time), noninvasive, repeatable, and cost-effective.
Copyright © 2012 The Obesity Society.
1 Communities
3 Members
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14 MeSH Terms
Relationships between serum adiponectin and bone density, adiposity and calcified atherosclerotic plaque in the African American-Diabetes Heart Study.
Register TC, Divers J, Bowden DW, Carr JJ, Lenchik L, Wagenknecht LE, Hightower RC, Xu J, Smith SC, Hruska KA, Langefeld CD, Freedman BI
(2013) J Clin Endocrinol Metab 98: 1916-22
MeSH Terms: Adiponectin, Adiposity, African Americans, Aged, Body Mass Index, Bone Density, Bone Resorption, C-Reactive Protein, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Humans, Intra-Abdominal Fat, Male, Middle Aged, North Carolina, Obesity, Plaque, Atherosclerotic, Severity of Illness Index, Sex Characteristics, Vascular Calcification
Show Abstract · Added February 15, 2014
CONTEXT - Adiposity, bone mineral density (BMD), and calcified atherosclerotic plaque (CP) exhibit complex interrelationships that are not well understood. Adipokines vary in relation to changes in body composition and may play roles in regulation of BMD and risk of cardiovascular disease.
OBJECTIVE - Our objective was to examine the relationship between serum adiponectin and quantitative computed tomography-derived measures of volumetric BMD (vBMD) in thoracic and lumbar vertebrae, adipose tissue volumes, and CP in coronary, carotid, and infrarenal aortoiliac arteries. Generalized linear models were fitted to test for associations between adiponectin and measured phenotypes.
PARTICIPANTS - A total of 479 unrelated African Americans with type 2 diabetes, 57% female with a mean ± SD (median) age of 55.6 ± 9.5 (55.0) years and diabetes duration of 10.3 ± 8.2 (8.0) years.
RESULTS - Serum adiponectin was 8.26 ± 7.41 (6.10) μg/mL, coronary artery CP mass score was 280 ± 634 (14), carotid artery CP was 47 ± 133 (0), and aortoiliac CP was 1616 ± 2864 (319). Women had significantly higher body mass index and serum adiponectin and lower coronary and carotid artery calcium than males (all P < .05). Before and after adjusting for age, sex, body mass index, mean arterial pressure, smoking status, hemoglobin A1c, thiazolidinedione use, and low-density lipoprotein-cholesterol, adiponectin was inversely associated with thoracic and lumbar vertebral vBMD [parameter estimates (PEs) of -0.06 and -0.021, respectively; both P < .0005], visceral adipose tissue (PE -0.02; P < 0.0001), and C-reactive protein (PE -0.07; P < .0001) and positively associated with intermuscular adipose tissue (PE 0.01; P = .03). After covariate adjustment, significant associations were not observed between adiponectin and CP in any vascular bed (P > .1).
CONCLUSION - Serum adiponectin levels were inversely associated with cross-sectional measures of thoracic and lumbar vertebral vBMD, inflammation, and visceral adiposity in African Americans but not with vascular CP after adjustment for covariates. The data support a regulatory/signaling role for adiponectin in the modulation of bone density.
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22 MeSH Terms
Differential associations of abdominal visceral, subcutaneous adipose tissue with cardiometabolic risk factors between African and European Americans.
Liu J, Coady S, Carr JJ, Hoffmann U, Taylor HA, Fox CS
(2014) Obesity (Silver Spring) 22: 811-8
MeSH Terms: African Americans, Aged, Blood Pressure, Body Mass Index, Cardiovascular Diseases, Cholesterol, HDL, Cross-Sectional Studies, Diabetes Mellitus, European Continental Ancestry Group, Female, Humans, Hypertension, Intra-Abdominal Fat, Linear Models, Logistic Models, Male, Metabolic Syndrome, Middle Aged, Multivariate Analysis, Obesity, Risk Factors, Subcutaneous Fat, Subcutaneous Fat, Abdominal, Triglycerides
Show Abstract · Added February 15, 2014
OBJECTIVE - To examine the relative association of abdominal visceral adipose tissue (VAT) with cardiometabolic risk factors between African and European Americans.
METHODS - A cross-sectional study of 2,035 African Americans from the Jackson Heart Study (JHS) and 3,170 European Americans from the Framingham Heart Study (FHS) who underwent computed tomography assessment of VAT and subcutaneous adipose tissue (SAT) was conducted. The FHS participants were weighted to match the age distribution of the JHS participants, and the metabolic risk factors were examined by study groups in relation to VAT.
RESULTS - JHS participants had higher rates of obesity, hypertension, diabetes, and metabolic syndrome than FHS participants (all P = 0.001). The associations were weaker in JHS women for VAT with blood pressure, triglycerides, HDL-C, and total cholesterol (Pinteraction = 0.03-0.001) than FHS women. In contrast, JHS men had stronger associations for VAT with high triglycerides, low HDL, and metabolic syndrome (all Pinteraction = 0.001) compared to FHS men. Similar associations and gender patterns existed for SAT with most metabolic risk factors.
CONCLUSIONS - The relative association between VAT and cardiometabolic risk factors is weaker in JHS women compared to FHS women, whereas stronger associations with triglycerides and HDL were observed in JHS men.
Copyright © 2013 The Obesity Society.
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24 MeSH Terms
Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.
Fox CS, White CC, Lohman K, Heard-Costa N, Cohen P, Zhang Y, Johnson AD, Emilsson V, Liu CT, Chen YD, Taylor KD, Allison M, Budoff M, CARDIoGRAM Consortium, Rotter JI, Carr JJ, Hoffmann U, Ding J, Cupples LA, Liu Y
(2012) PLoS Genet 8: e1002705
MeSH Terms: Adipose Tissue, Adult, African Continental Ancestry Group, Animals, Asian Continental Ancestry Group, Atherosclerosis, Body Fat Distribution, Body Mass Index, Calcium-Calmodulin-Dependent Protein Kinases, Coronary Disease, European Continental Ancestry Group, Female, Gene Expression Regulation, Genome-Wide Association Study, Hispanic Americans, Humans, Intra-Abdominal Fat, Intracellular Signaling Peptides and Proteins, Male, Mice, Middle Aged, Obesity, Pericardium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Tomography, X-Ray Computed
Show Abstract · Added February 15, 2014
Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.
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26 MeSH Terms
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
Fox CS, Liu Y, White CC, Feitosa M, Smith AV, Heard-Costa N, Lohman K, GIANT Consortium, MAGIC Consortium, GLGC Consortium, Johnson AD, Foster MC, Greenawalt DM, Griffin P, Ding J, Newman AB, Tylavsky F, Miljkovic I, Kritchevsky SB, Launer L, Garcia M, Eiriksdottir G, Carr JJ, Gudnason V, Harris TB, Cupples LA, Borecki IB
(2012) PLoS Genet 8: e1002695
MeSH Terms: Adult, Aged, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Mass Index, Cytokines, European Continental Ancestry Group, Female, Genome-Wide Association Study, HapMap Project, Humans, Intra-Abdominal Fat, Lysophospholipase, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proteins, Sex Characteristics, Subcutaneous Fat, Abdominal
Show Abstract · Added February 15, 2014
Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.
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19 MeSH Terms